A First-in-Human, JAB-8263 in Adult Patients With Advanced Tumors

• Sponsor: Jacobio Pharmaceuticals Co., Ltd. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04686682
• Collaborator: (none)
• Enrollment: 152
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 27.8
• Patients Per Site Per Month: 5.5

Study Details

Study Description

Brief Summary

This is a Phase 1/2a, first-in-human, open-label study of JAB-8263, this study has two parts:

solid tumor dose escalation and expansion study and hematology tumor dose escalation and expansion study.

These two parts will determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D) and assess the DLT of JAB-8263 in treatment with patients with advanced solid tumors and hematology tumors separately. 30 subjects each will be enrolled.

Condition or Disease	Intervention/Treatment	Phase
NSCLC; SCLC; CRPC; ESCC; Ovarian Carcinoma; AML; MF; Malignant Tumor	Drug: JAB-8263; Drug: JAB-8263	Phase 1/Phase 2

Detailed Description

JAB-8263 is a small-molecule inhibitor of the highly conserved bromodomain pockets of the bromodomain and extraterminal (BET) proteins.

The objectives of this study are:

To determine the maximum-tolerated dose (MTD) and assess the dose-limiting toxicity (DLT) of JAB-8263 as a single agent to adult subjects with advanced malignant tumors. To assess the safety and tolerability of JAB-8263 To characterize the pharmacokinetic (PK) parameters and pharmacodynamics (PDc).To evaluate preliminary antitumor activity of JAB-8263

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 152 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/IIa, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-8263 in Adult Patients With Advanced Malignant Tumors
• Actual Study Start Date: May 7, 2021
• Anticipated Primary Completion Date: Jan 1, 2023
• Anticipated Study Completion Date: Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: JAB-8263 Part1 Monotherapy, dose escalation	Drug: JAB-8263; Variable dose, orally Q2D with 28 days each cycle
Experimental: JAB-8263 Part 2 Monotherapy, dose expansion	Drug: JAB-8263; RP2D dose, orally Q2D with 28 days each cycle

Outcome Measures

Primary Outcome Measures

1. Number of participants with dose limiting toxicities [Approximately 18 months]

   Incidence of dose limiting toxicities (DLTs) in the dose escalation phase. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first treatment cycle with JAB-8263

Secondary Outcome Measures

1. Number of participants with adverse events [Approximately 18 months]

   All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs, electrocardiograms, cardiac imaging and ophthalmological assessments

2. Area under the curve [Approximately 18 months]

   Area under the plasma concentration time curve of JAB-8263

3. Cmax [Approximately 18 months]

   Highest observed plasma concentration of JAB-8263

4. Tmax [Approximately 18 months]

   Time of highest observed plasma concentration of JAB-8263

5. T1/2 [Approximately 18 months]

   Half life of JAB-8263

6. Objective response rate ( ORR ) [Approximately 18 months]

   For solid tumor study part, ORR is defined as the proportion of participants with complete response or partial response (CR+PR)

7. Duration of response ( DOR ) [Approximately 18 months]

   For solid tumor study part, DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first.

8. Duration of response ( DCR ) [Approximately 18 months]

   For solid tumor study part, DCR is defined as proportion of participants with complete response, partial response, stable disease(CR+PR+SD).

9. CR without minimal residual disease rate (CR MRD-) [Approximately 18 months]

   hematology study part, CR MRD- is defined as proportion of participants with complete response without minimal residual disease.

10. Overall response rate [Approximately 18 months]

    For hematology study part, Overall response rate is defined as proportion of participants with complete response(CR or CRi), partial remission(PR) or morphologic leukemia-free state(MLFS).

11. Event-free survival( EFS) [Approximately 18 months]

    For hematology study part, EFS is defined for all patients with AML, measured from the date of entry into the study to the date of primary refractory disease, or relapse from CR, or Cri, or death from any cause.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must meet all the following criteria in order to be included in the research study:

1. Subject must be ≥18 years-of-age at the time of signature of the informed consent form (ICF).

2. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.

3. Subjects with histologically or cytologically confirmed advanced solid tumors which have progressed despite standard therapy(ies), or are intolerant to standard therapy(ies), or have a tumor for which no standard therapy(ies) exists.

4. Subjects with recurrent/refractory AML according to WHO 2016

5. Subjects with life expectancy ≥3 months.

6. Patients with solid tumor must have at least one measurable lesion as defined by RECIST v1.1.

7. Patients who have sufficient baseline organ function.

Exclusion Criteria:

1. History (≤3 years) of cancer that is histologically distinct from the cancer under study.

2. Known serious allergy to investigational drug or excipients

3. Active brain or spinal metastases

4. History of pericarditis or Grade ≥2 pericardial effusion

5. History of interstitial lung disease.

6. History of Grade ≥2 active infections within 2 weeks

7. Known human immunodeficiency virus (HIV) infection

8. Seropositive for hepatitis B virus (HBV)

9. Seropositive for hepatitis C virus (HCV), or HCV-RNA viral levels are not detectable.

10. Any severe and/or uncontrolled medical conditions

11. History of myocardial infarction, unstable angina pectoris, coronary artery bypass graft, or cerebrovascular accident

12. Impaired cardiac function or clinically significant cardiac diseases

13. QTcF >470 msec at screening

14. History of medically significant thromboembolic events or bleeding diathesis

15. Unresolved Grade >1 toxicity

16. History of malignant biliary obstruction

17. Pregnant or breast-feeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tianjin	Tianjin	Tianjin	China	300020

Sponsors and Collaborators

• Jacobio Pharmaceuticals Co., Ltd.

Investigators

• Study Director: Jacobio Pharmaceuticals, Jacobio Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jacobio Pharmaceuticals Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04686682
• Other Study ID Numbers: JAB-8263-1002
• First Posted: Dec 29, 2020
• Last Update Posted: Mar 14, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neoplasms

Study Results

No Results Posted as of Mar 14, 2022